A dynamic network approach for the study of human phenotypes

TL;DR

This paper introduces a large phenotypic network derived from over 30 million patient records, demonstrating how disease progression and patient outcomes are related to the network's structure, thus providing new insights into human disease evolution.

Contribution

The paper presents a novel, large-scale phenotypic database and network model that links disease progression with network topology and patient demographics, advancing disease understanding.

Findings

Patients develop diseases close to their existing conditions in the network.

Disease progression patterns vary by gender and ethnicity.

Highly connected diseases are associated with higher mortality.

Abstract

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.